The entrapment neuropathies are the most common type of neuropathies affecting man and cause major personal and economic impact. We have developed a model of chronic entrapment in rats and rabbits which regularly cause focal demyelination. Methodology has been developed in this laboratory to directly measure endoneurial fluid pressure and blood flow within the entrapped region. By relating endoneurial fluid pressure and blood flow values to the focal pathologic changes, it will be possible to directly test the hypothesis that entrapment induced demyelination is caused by local and focal collapse of capillaries or other ischmic mechanisms. By systematically relating pressure: volume changes to axon volume and shape changes at multiple levels using detailed morphometry it will be possible to define the type an quantity of biophysical stresses that cause demyelination. This approach has previously not been possible. Peripheral nerve perineurium is distorted at the cuff edge and should perineurial permeability or compliance become abnormal at these regions there may occur an influx of potentially neurotoxic compounds into the endoneurium of nerve. We plan to directly measure perineurial compliance of the entrapped region using a sensitive in vitro active servo-null system and to test if permeability is increased using two isotopes (C14 sucrose, I125 albumin) in entrapped and normal fibers and the same fibers when stressed to 5 mm mercury. The endoneurial fluid pressure and morphometric studies will be performed in year 1, compliance and permeability studies in year 2 and intrafascicular blood flow studies in year 3.